Solid mammary tumors are induced in nude mice by s.c. injections of the human breast cancer cell lines MCF-7 or ZR-75. Tumor induction is estrogen dependent, and prolactin (but not progesterone) appears to also have a stimulatory effect. The high frequency of lung, spleen and liver metastases makes this system particularly useful in the ongoing study on the mechanism of basement membrane invasiveness by tumor cells and the role of hormone both in vivo and in vitro in this process. Tumor growth proceeds even when the tumor host is ovariectomized but tumors regress when the host is treated with antiestrogens. This raised the possibility that these tumor cells continue to be estrogen dependent but have the potential of making their own hormones. We are investigating the possibility of a paraendocrine activity by these cells and their solid tumors and are in the process of designing experiments on combined endocrine and chemotherapeutic protocols that could induce an appropriate and most effective tumor regression.